期刊
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
卷 495, 期 1, 页码 174-178出版社
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.bbrc.2017.10.163
关键词
Reactive nitrogen species (RNS); Reactive oxygen species (ROS); Ergothioneine (ERG); Mycothiol (MSH); Gamma-glutamylcysteine (GGC); Glutathione (GSH)
资金
- South African Medical Research Council (SAMRC)
- DST-NRF Centre of Excellence in Biomedical Tuberculosis Research
- Harry Crossley Foundation [SU-PT-15/09-000028]
Mycobacterium tuberculosis (M.tb.), the causative agent of tuberculosis (TB), cannot synthesize GSH, but synthesizes two major low molecular weight thiols namely mycothiol (MSH) and ergothioneine (ERG). Gamma-glutamylcysteine (GGC), an intermediate in GSH synthesis, has been implicated in the protection of lactic acid bacteria from oxidative stress in the absence of GSH. In mycobacteria, GGC is an intermediate in ERG biosynthesis, and its formation is catalysed by EgtA (GshA). GGC is subsequently used by EgtB in the formation of hercynine-sulphoxide-GGC. In this study, M.tb. mutants harbouring unmarked, in-frame deletions in each of the fives genes involved in ERG biosynthesis (egtA, egtB, egtC, egtD and egtE) or a marked deletion of the mshA gene (required for MSH biosynthesis) were generated. Liquid chromatography tandem mass spectrometry analyses (LC-MS) revealed that the production of GGC was elevated in the MSH-deficient and the ERG-deficient mutants. The ERG-deficient Delta egtB mutant which accumulated GGC was more resistant to oxidative and nitrosative stress than the ERG-deficient, GGC-deficient Delta egtA mutant. This implicates GGC in the detoxification of reactive oxygen and nitrogen species in M.tb. (C) 2017 Elsevier Inc. All rights reserved.
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